This company is all about what we do with that genetic data after we got it.
1/ The sequencing companies make the machines to actually sequence the DNA or RNA. $NVTA is about taking that genetic data and translating it into something that can be used my medical professionals to treat patients.
2/ This is about using automation, software and a database to use the genetic data acquired by the sequencing. I call this the Genomics Application company.
3/ This company is about using genetic data across all stages of life and all stages of treatment to personalize therapies specifically to each patient. They working to drive down costs of genetic testing so everyone can be tested.
4/ Their second goal is to build the database of genetic information that can be used globally to help guide treatments, research and new therapies. Its about the totality of the genetics across the population and how it can be used.
5/ Building out all the necessary resources to bring together all the tech, software and database has driven their costs over the past few years.
6/ They have done many acquisitions of smaller companies to help build their platform. This is a lot of short term spending to drive the long term opportunity.
7/ This is a space of the science where a first mover can dominate the industry like a Google or Microsoft.
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They are building the best long and short read company in sequencing.
1/ They already have the long read sequencing with the SMRT technology. They have an install base of 326 instillations as of Q3. That has a lot of potential to grow. Half their revenues comes from the selling of the consumables that goes into running those devices.
2/ As the Base grows, this becomes like the Apple model with and ecosystem. They buy the device and then you earn revenue off the use of that device.
Digging into how Single Molecule, Real Time (SMRT) technology.
1/ The SMRT technology takes advantage of DNA synthesis. To understand it, we must do a brief review of DNA synthesis. When DNA gets copied, a single strand of DNA gets copied by the DNA polymerase enzyme.
2/ The nucleotides are picked up by the DNA polymerase and incorporated into the new strand of DNA that is being built that is an exact opposite copy of the template strand.
Taking a look at the use of CRISPR CAS9 use in ex-vivo cell therapies.
1/ $CRSP is using the same CRISPR/CAS9 system as $NTLA. This is made up of the CAS9 enzyme which has 2 nuclease domains that do the cutting of the DNA into a Double Stranded Break. It also includes a guide RNA for searching the DNA for the correct site.
2/ The biggest danger of the CAS9 enzyme is that cuts both strands of the DNA at the same location. Without the use of a template strand, this will trigger Non Homologous End Joining which is a very inaccurate process.
Taking a look the science behind CRISPR CAS9 and in-vivo liver editing.
1/ $NTLA is using the CRISPR/CAS9 system. This is made up of the CAS9 enzyme which has 2 nuclease domains that do the cutting of the DNA into a Double Stranded Break. It also includes a guide RNA for searching the DNA for the correct site.
2/ The biggest danger of the CAS9 enzyme is that cuts both strands of the DNA at the same location. Without the use of a template strand, this will trigger Non Homologous End Joining which is a very inaccurate process.
Taking a look at the preclinical data for their programs so far.
1/ They have two main programs around correcting Sickle Cell disease. Their first program BEAM-101 is doing a simple gene knockout on the gene that suppresses Fetal Hemoglobin expression causing the reactivation of the Fetal Hb gene.
2/ Their second program uses base editing to change the defective base in the Sickling Hemoglobin to a Makassar that works normally.
This will be a look at the underlying technology of base editing. I plan another guide for the science and maybe another for the corporate.
1/ They are using base editing technology. This takes the CRISPR CAS9 enzyme along with the guide RNA attached to a deaminase enzyme to make a modification to a single base of the DNA.
2/ The guide RNA looks for a photospacer sequence in the DNA. That is just a matching sequence of DNA that matches the guide RNA. Next to the photospacer sequence will the the Photospacer adjacent motif (PAM).